Update on Eisenmenger syndrome – Review of pathophysiology and recent progress in risk assessment and management

Longstanding left-to-right shunting associated with congenital heart disease (CHD) can ultimately lead to pulmonary vascular remodeling, pulmonary arterial hypertension, and shunt reversal, the hallmark feature of Eisenmenger Syndrome (ES). ES is a multisystem disease, with hematologic, cardiovascular, renal, neurologic, immune, and other manifestations, each of which inform its management. Many of the most distinct and clinically important consequences relate to chronic hypoxemia. The incidence of ES in in countries with access to pediatric cardiology and cardiac surgery services has declined in recent decades, due to earlier diagnosis and intervention for CHD. Moreover, in the era of disease targeting therapies (DTT), ES appears to be associated with better quality of life and less limiting symptoms. In addition, observational studies suggest that these therapies, alone and in combination, may be associated with improved survival. Despite these developments, ES mortality remains high, with heart failure being the most common cause of death. In this review, we discuss the pathophysiology of ES, the evolving understanding of risk stratification, as well as recent progress in pharmacologic and surgical management. Ultimately, despite strides in understanding and management of this complex disease, significant knowledge gaps remain.